RhoA signaling: the nanoscale mechanisms of mechanochemical regulation. This project aims to elucidate a new paradigm for regulating cell signals at the nanoscale level. Cell signalling involves the coordination of multi-molecular networks at the plasma membrane, the interface between the cell and its external environment. These are often thought to involve the assembly of multimolecular complexes through the action of protein scaffolds. This project will focus on how the contractile regulator, ....RhoA signaling: the nanoscale mechanisms of mechanochemical regulation. This project aims to elucidate a new paradigm for regulating cell signals at the nanoscale level. Cell signalling involves the coordination of multi-molecular networks at the plasma membrane, the interface between the cell and its external environment. These are often thought to involve the assembly of multimolecular complexes through the action of protein scaffolds. This project will focus on how the contractile regulator, anillin, controls RhoA signalling by kinetic regulation. In particular, how nanoscale clustering of anillin by the dynamic actomyosin cytoskeleton modulates RhoA signalling for contractility and tissue homeostasis. The outcomes of this project are first and foremost fundamental understanding of how cells communicate with one another.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100558
Funder
Australian Research Council
Funding Amount
$389,220.00
Summary
Caveolae as structural mechanosensors: a link between the intra and extracellular environments? How cells perceive and respond to mechanical cues are fundamental questions in cellular biology. Caveolae are invaginations of the plasma membrane which flatten into the bulk membrane in response to increased membrane tension. This project aims to validate this response at the molecular level in a physiological context. Specifically, the project will investigate how the caveola response coordinates wi ....Caveolae as structural mechanosensors: a link between the intra and extracellular environments? How cells perceive and respond to mechanical cues are fundamental questions in cellular biology. Caveolae are invaginations of the plasma membrane which flatten into the bulk membrane in response to increased membrane tension. This project aims to validate this response at the molecular level in a physiological context. Specifically, the project will investigate how the caveola response coordinates with the extracellular matrix as well as study the fate of caveolar proteins released from caveolae. Besides the establishment of new methodologies, the findings will highlight the role of caveolae in the short and long term adaptive responses to mechanical cues and enhance understanding of how cells integrate the extracellular and intracellular environments.Read moreRead less
Defining mechanisms behind the formation of hierarchical vascular networks. Blood vessels form complex branched networks composed of arteries, capillaries and veins. The development and maintenance of different vessel systems (arteries and veins) is dependent on cell adherence properties within each vessel, yet how these are established and maintained remains unknown. This project aims to analyse the differences in junctional dynamics between sprouting arteries and veins, and to identify arteria ....Defining mechanisms behind the formation of hierarchical vascular networks. Blood vessels form complex branched networks composed of arteries, capillaries and veins. The development and maintenance of different vessel systems (arteries and veins) is dependent on cell adherence properties within each vessel, yet how these are established and maintained remains unknown. This project aims to analyse the differences in junctional dynamics between sprouting arteries and veins, and to identify arterial and venous signalling networks that make and maintain vessel identity. This project will reveal how adhesiveness is regulated in order to make a hierarchical, functional vascular network, with implications for engineering of functional, vascularised organs in the biotech sector.Read moreRead less
The core inflammasome as a model for caspase activation. This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. This project proposes the speck is a terminal stage, after the major enzymatic activity is over. This project aims to purify sma ....The core inflammasome as a model for caspase activation. This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. This project proposes the speck is a terminal stage, after the major enzymatic activity is over. This project aims to purify smaller early stage inflammasome complexes, for structural analysis. The outcome will be a clearer understanding of processes of caspase activation and inflammasome formation. This will provide significant benefits, such as improve our understanding of processes of cell death and innate immunity, and train students.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less
Mechanotransduction: a new paradigm for cadherin junction biology. Cell adhesion is necessary to hold the cells in our tissue together, and is essential for organ function. It is essential for adhesion junctions to resist force that would break them apart. This project investigates how adhesion junctions sense and respond to force acting on cells.
Interrogating a novel protein scaffold that coordinates signal transduction and molecular motor function. The inside of a cell is an extremely crowded environment and the precise location of each component is carefully controlled. This project will unravel the protein machinery involved in transporting cargos in cells as they divide and identify new protein targets for the development of next generation anti-cancer drugs.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100163
Funder
Australian Research Council
Funding Amount
$560,000.00
Summary
Single molecule imaging laboratory. Single molecule imaging laboratory: The goal of the project is to establish a single molecule imaging laboratory to close the gap between structural imaging and cellular imaging. Utilising the expertise of the ARC Centre of Excellence in Advanced Molecular Imaging, the aim of the project is to design, build and apply three microscopes that go beyond the current commercial solutions for single molecule localisation microscopy such as Photo-Activation Localisati ....Single molecule imaging laboratory. Single molecule imaging laboratory: The goal of the project is to establish a single molecule imaging laboratory to close the gap between structural imaging and cellular imaging. Utilising the expertise of the ARC Centre of Excellence in Advanced Molecular Imaging, the aim of the project is to design, build and apply three microscopes that go beyond the current commercial solutions for single molecule localisation microscopy such as Photo-Activation Localisation Microscopy (PALM) and Stochastic Optical Reconstruction Microscopy (STORM) and perform single molecule imaging: deep inside cells and tissue.The facility will have a fast acquisition rate to monitor highly dynamic molecular events, and improved precision to image molecules and complexes in intact cells with less than or equal to one nanometre resolution. There is currently no comparable imaging facility in the world.Read moreRead less
How filopodia connect macrophages to the outside world. Fundamental to life is the ability of cells to sense their surroundings and respond accordingly. This project aims to generate a biological understanding of how certain immune cells carry out such processes, thus enabling them to combat infections.
A role for the actin cytoskeleton in suppression of prion pathology in yeast. The discovery that proteins as well as DNA carry genetic information is leading to a re-think of the mechanisms that program cell behaviour. There is a link between proteins that suppress cancer and protein inheritance. This project explores how heritable changes in proteins control cell behaviour and the implications of this for the origin of cancer.